Identification of cervical intraepithelial neoplasia (CIN) using UV-excited fluorescence and diffuse-reflectance tissue spectroscopy.

BACKGROUND AND OBJECTIVE: The diagnostic potentials of ultraviolet-excitation fluorescence spectroscopy and diffuse-reflectance spectroscopy of tissue are assessed in a study to identify cervical intraepithelial neoplasia (CIN) in vivo. A multivariate algorithm is used to classify tissue into normal tissues, CIN I, and CIN II/III categories, based on spectral characteristics of biopsied tissue sites. STUDY DESIGN/MATERIALS AND METHODS: An optical instrument with the capability of measuring fluorescence and diffuse-reflectance spectra from 120 locations uniformly distributed over the surface of the cervix is described. Using this device, these optical spectra of the cervix were measured on women referred for colposcopy due to an abnormal Pap smear. RESULTS: UV fluorescence differentiates CIN II/III lesions from normal squamous tissue with a sensitivity and specificity of 91 and 93%, respectively. CIN I is distinguished from normal tissue with a sensitivity of 86% and a specificity of 87%. CONCLUSION: Optical spectroscopy shows promise for the detection of pre-cancerous cervical lesions in vivo. The fluorescence and reflectance methods are complementary in their ability to differentiate different tissue types, making the use of the two techniques together more diagnostic than the use of either method separately.

Early discharge after abdominal surgery: experience on a gynecologic oncology service.

OBJECTIVES: The goals of this study were to determine the length of stay (LOS) after abdominal surgery following implementation of practice guidelines on a gynecologic oncology service, to identify adverse outcomes of early discharge, and to identify clinical predictors of longer LOS. METHODS: A retrospective chart review of 266 consecutive patients who had elective abdominal surgery was performed. Clinical data, LOS, and follow-up data were abstracted. Univariate and multivariate analyses were performed to identify clinical variables predictive of LOS. RESULTS: Mean LOS was 2.94 days. Seven (2.6%) patients were readmitted after discharge. With multivariate analysis, extensive surgical procedures, coronary artery disease, and bowel surgery were predictive of longer LOS (P < 0.05). CONCLUSIONS: Early discharge following abdominal surgery was possible for most patients and was associated with a low rate of readmission. Extensive surgical procedures, coronary artery disease, and bowel surgery were predictive of longer LOS.

Outpatient minilaparotomy for ovarian cysts.

OBJECTIVE: To design an operative procedure for the ambulatory management of ovarian cysts using classical surgical techniques. STUDY DESIGN: One hundred consecutive patients 55 years old or younger with 115 persistent or complex ovarian cysts less than 10 cm in diameter were managed as outpatients by minilaparotomy. Minilaparotomy is defined as a transverse or vertical incision 3-5 cm in length. The procedure and anesthetic were dictated by each clinical situation. Bupivacaine HCl with epinephrine was injected in the wound preemptively, and ketorolac was administered systemically perioperatively. Operative times, complications and pathology were determined for each case. RESULTS: The procedures (unilateral cystectomy, 65; bilateral cystectomy, 9; unilateral salpingo-oophorectomy, 20; and bilateral salpingo-oophorectomy, 6) were performed under general endotracheal anesthesia in 89, laryngeal mask anesthesia in 5 and spinal block in 6. Mean operative time was 46 minutes. Estimated blood loss in 96% of cases was < 50 mL, and none was > 100 mL. Pathology in two cases revealed adenocarcinoma of borderline malignancy. Remaining histology included endometrioma, 40; dermoid, 25; serous cystadenomas, 14; hemorrhagic corpus luteum, 9; mucinous cystadenoma, 8; cystadenofibroma, 7; follicular cyst, 3; fibrothecoma, 2; and peritoneal inclusion cyst, 1. Ninety-six of 100 patients were discharged on the day of surgery. Two were admitted for urinary retention, one for severe nausea and vomiting, and one for diabetes control. CONCLUSION: Minilaparotomy is a safe, rapid procedure for the management of ovarian cysts on an ambulatory basis. It can be performed under regional anesthesia, avoids intraperitoneal spill and requires only basic operative techniques and instrumentation. Minilaparotomy is also a cost-effective technique for outpatient management of ovarian cysts.

Incidence and predictors of cervical dysplasia in patients with minimally abnormal Papanicolaou smears.

OBJECTIVE: To estimate the incidence of dysplasia in patients with Papanicolaou smears showing atypical squamous cells of undetermined significance (ASCUS) and low-grade squamous intraepithelial lesions (SIL) and to identify clinical predictors of dysplasia in these patients. METHODS: Patients referred for ASCUS and low-grade SIL were reviewed retrospectively. All patients were evaluated with immediate colposcopy. A multivariate logistic regression analysis was performed to identify clinical predictors of histologic SIL and histologic high-grade SIL. RESULTS: One hundred thirty-seven (34%) of 406 consecutive patients had histologic SIL. Regression analysis identified age (under 35 versus 35 years or above) and initial smear (low-grade SIL versus ASCUS) as statistically significant predictors of histologic SIL and high-grade SIL (P < .001). When patient outcomes were analyzed by age and initial Papanicolaou smear results, the subgroup of patients 35 years or older with ASCUS had low incidences of histologic SIL (14%) and high-grade SIL (1%). The other subgroups (under 35 years with ASCUS, under 35 years with low-grade SIL, and 35 years or older with low-grade SIL) had incidences of histologic SIL and histologic high-grade SIL of at least 28% and 14%, respectively. CONCLUSION: The high incidence of dysplasia in patients with minimally abnormal Papanicolaou smears suggests that immediate colposcopy might be appropriate for many of these patients. Age and initial Papanicolaou smear are predictive of dysplasia and might be used to select patients who have low incidence of dysplasia and might not require immediate colposcopy.

Endometrial carcinoma: analysis of recurrence in patients treated with a strategy minimizing lymph node sampling and radiation therapy.

OBJECTIVE: To determine whether using a treatment strategy minimizing lymph node sampling and radiation therapy compromised outcome in patients with early endometrial carcinoma. METHODS: One hundred three consecutive patients with International Federation of Gynecology and Obstetrics surgical stage I, II, or III endometrial carcinoma were treated with primary surgery followed by tailored adjuvant radiation therapy using a strategy designed to minimize lymph node sampling and whole pelvic radiation. Para-aortic lymph node dissection was performed only among patients with high-risk factors such as high-grade tumors, deep myometrial invasion, or stage II or III disease. Postoperative radiation therapy was tailored to the surgical and pathologic findings. Treatment with whole pelvic radiation was limited to patients with at least one of these high-risk factors. RESULTS: Thirty-four patients underwent para-aortic node dissection. Thirty-six patients received no adjuvant radiation therapy; 19 received vaginal radiation and 47 received whole pelvic radiation. Ninety-three patients (90%) have had no tumor recurrence during a median follow-up period of 30 months (range 8-96). Analysis of the recurrence pattern indicates that more aggressive use of lymph node evaluation or radiation therapy would not have lowered the recurrence rate. All of the patients who had recurrence were identified as high-risk and received aggressive therapy. Furthermore, the pattern of recurrence suggests that many of these patients had occult distant disease at the outset of therapy. CONCLUSION: The data suggest that this selective approach does not compromise survival in patients with early-stage endometrial carcinoma. This management strategy has the advantage of confining the morbidity of lymph node dissection and radiation therapy to those patients at greatest risk for lymph node metastases and recurrence, respectively. Further improvements in survival await the development of effective systemic therapy.

Relationship between obesity and uterine leiomyomata.

Obesity is associated with many comorbid disease states including neoplasia. The increased risk of developing endometrial cancer is thought to be due to the higher level of circulating estrogens in obese women. Uterine leiomyomata (fibroids) are also thought to be influenced by estrogens. To determine whether patients presenting with symptomatic uterine fibroids were more obese than the general population, we retrospectively reviewed the hospital records of 144 women who underwent either hysterectomy or myomectomy for uterine fibroids. Obesity was defined as preoperative weight greater than 120% of desirable body weight (DBW) for the patient's height. In our investigation, 51% of the study population were obese. Moreover, 16% were severely obese (defined as greater than 150% DBW). When compared with the general population of women in the United States matched for height and age, the study population was significantly heavier. (p less than 0.0002). Patient age, parity, menopausal status, and degree of obesity did not correlate with the number of fibroids within the uterus. Fibroid size was significantly larger in nulliparous women (p less than 0.005). These results suggest that symptomatic uterine fibroids may be another comorbid disease state associated with obesity.

Ovarian malignancy.

Despite major advances in the management of ovarian cancer over the last two decades, overall prognosis remains poor. Attempts to improve early detection by screening with sonography and tumor markers have thus far been unsuccessful. The tumor marker CA-125 has, however, proven to be useful in indicating responsiveness to chemotherapy, and in turn predicts survival. Patients with well- or moderately well-differentiated stage IA-1 and IB-1 ovarian cancers have excellent survivals and do not require adjuvant therapy. In contrast, patients with poorly differentiated stage I and II tumors have a 20% failure rate and should be treated. Carboplatinum, with its favorable spectrum of toxicities, is becoming the platinum analogue of choice. Taxol is a new active agent for ovarian cancer and may prove efficacious in combination with platinum for ovarian cancer. Second-look surgery should no longer be performed routinely. Recent data suggest that tumor heterogeneity may compromise immunotherapy that targets cell surface antigens.

Antigenic heterogeneity in human ovarian cancer.

Primary and metastatic tumor tissues from 21 patients with ovarian epithelial cancer were studied with a panel of 8 monoclonal antibodies. Primary tumors reacted with 1 to 7 antibodies (mean, 3.5). Heterogeneity was observed even within histologic subtypes. Comparison of metastases (including ascites) with their respective primaries revealed differences in antigen profile in each of 10 cases studied. In one patient variable antigen expression was observed in five ascites samples collected over a 12-month period. These observations of antigenic heterogeneity and modulation with respect to site and time suggest that single monoclonal antibody immunotherapy would not be appropriate for all patients or even for a single patient over time.

Adenocarcinoma of the cervical stump.

Sixteen women with adenocarcinoma of the cervical stump were treated over a 15-year period. The median survivals of 40 months for stage IB and 17 months for stages II and III were significantly worse compared with those for patients treated for cervical adenocarcinoma of the intact uterus or squamous carcinoma of the cervical stump. The poor results were due to both local and distant failure. Implications regarding tumor radiosensitivity and adjuvant therapy in these high-risk patients are discussed.

Adenocarcinoma of the uterine cervix: prognostic factors and patterns of recurrence.

Survival data, prognostic factors, and patterns of recurrence were analyzed for 70 women with adenocarcinoma of the uterine cervix treated between 1968 and 1982. The 5-year survival rates for stages I, II, and III-IV were 82, 90, and 38%, respectively. Control of pelvic tumor was achieved in 82, 80, and 12.5% of cases of stage I, II, and III-IV disease, respectively. When radiation therapy techniques alone were employed, pelvic control was achieved in 100% of stage I and 75% of stage II cases. Tumor grade was an important prognostic factor in stage I disease, with 92% of patients with grade 1 and 2 lesions surviving 5 years, in contrast to 68% of patients with grade 3 lesions (P less than 0.05, log rank test).

The role of the CA 125 assay in the management of ovarian cancer.

The monoclonal antibody-based serum assay for CA 125 is a reliable indicator of tumor status in patients with ovarian cancer. This noninvasive technique also permits individualization of therapy as well as early detection of recurrence. CA 125 levels are elevated in over 80% of patients with epithelial ovarian cancers. While the level of CA 125 also is elevated in some patients with benign disease, nevertheless this assay can help differentiate benign from malignant pelvic masses, using 35 U/ml as a normal reference value. Rising, stable, or falling levels correlate with tumor progression, stability, or regression in over 90% of cases, though a rising CA 125 level may be a more reliable predictor than a falling level. Evaluation of serial CA 125 levels during initial chemotherapy is a good indicator of a patient's response to therapy as well as a good predictor of eventual outcome. Because of its high specificity, it is also hoped that the CA 125 assay will soon be used to screen for ovarian cancer.

Whole abdominal irradiation for tumors of the uterine corpus.

Between November 1981 and December 1985, 16 patients with high-risk tumors of the uterine corpus were treated with a postoperative course of whole abdominal-pelvic irradiation. Thirteen patients had carcinomas and three had sarcomas. All patients had complete pelvic surgery including extrafascial (or modified radical) hysterectomy and bilateral salpingo-oophorectomy, pelvic node sampling, evaluation of peritoneal cytology, and resection of extrauterine metastases when indicated. All patients were free of gross visible tumor after surgery. Target doses of radiation were 3000 cGy to the upper abdomen and 4500 cGy to the pelvis. Median follow-up was 24 months for survivors (range, 17 to 63 months). The disease-free survival and overall survival at 17 months was 50%. Six of the 16 (38%) patients suffered intraabdominal relapse. One patient had a significant complication (bowel perforation). The data from this pilot study suggest that whole abdominal-pelvic irradiation may be useful only in the management of some patients with few high risk features of endometrial carcinoma. Patients with extensive extra-uterine involvement and with sarcoma histology do not appear to benefit from this experimental therapy.

Late recurrence in endometrial carcinoma.

This report describes a patient with a recurrence of endometrial carcinoma 26.5 years after diagnosis, a much longer interval to recurrence than previously reported. She presented at age 47 years with an International Federation of Gynecology and Obstetrics (FIGO) grade 2, Stage IA adenoacanthoma and was treated with an intracavitary radium implant followed by radical hysterectomy. Pathologic examination showed the tumor to be confined to the corpus with only superficial myometrial invasion. She subsequently developed an isolated lower vaginal recurrence histologically identical to the original tumor. The patient was retreated with radiation therapy, and is currently alive and free of disease. This report emphasizes the possibility of late recurrence of endometrial carcinoma even with favorable prognostic features (Stage I, superficial invasion, younger than age 50 years, adenoacanthoma, preoperative irradiation).

The CA 125 assay as a predictor of clinical recurrence in epithelial ovarian cancer.

Serum CA 125 levels were obtained from 55 women with epithelial ovarian cancer before a second-look surgical procedure and serially thereafter. All patients were clinically and radiographically free of tumor at the time of the second-look operation and were followed to clinical recurrence. Median follow-up was 12 months. CA 125 levels obtained at the second-look operation had a sensitivity and specificity for predicting clinical recurrence of 94% and 88%, respectively. Patients with an elevated CA 125 level (greater than or equal to 35 U/ml) had a 60% chance of clinical recurrence within 4 months, while patients with levels less than 35 U/ml had a 5% chance of clinical recurrence over the same time period. Serial CA 125 levels obtained after second-look operations were strong predictors of clinical outcome, and distinctly different monitoring profiles were observed among those patients remaining clinically free of tumor and those suffering clinical recurrence. The CA 125 assay became elevated (greater than or equal to 35 U/ml) before clinical recurrence in 94% of 35 cases with a median lead time of 3 months. The CA 125 assay identifies patients destined to suffer a clinical recurrence and provides a warning measurable in months. This may have important implications for therapy.

CA 125 serum levels correlated with second-look operations among ovarian cancer patients.

CA 125, which is an antigenic determinant expressed by many epithelial ovarian cancers, is measured in serum using a solid phase immunoradiometric assay. Sera from 55 patients who were in clinical remission and underwent a second-look operation to assess disease status after chemotherapy were studied prospectively. All patients had the CA 125 assay performed within one week before their second-look operation. Twenty-four patients (44%) had no histologic or cytologic evidence of disease, seven patients (13%) had microscopic disease, 13 patients (24%) had disease measuring 1 mm to 1.5 cm, and ten patients (18%) had disease greater than or equal to 1.5 cm in maximum tumor dimension. None of the 24 patients with a negative second-look operation had a positive CA 125 antigen level (greater than or equal to 35 U/mL), compared with six of 20 patients (30%) with less than 1.5 cm disease, and six of ten (60%) with greater than or equal to 1.5 cm disease (P less than .0001). All 12 patients with an elevated CA 125 antigen level (greater than or equal to 35 U/mL) had disease discovered at their second-look operation. Thus, in this setting the predictive value of a positive CA 125 titer (greater than or equal to 35 U/mL) was 100%. The predictive value of a negative CA 125 antigen level (less than 35 U/mL) was 56%, ie, the test did not exclude the presence of disease in 44% of patients with a positive second look. The maximum tumor size associated with at least one prior negative antigen level was 1.9 cm.(ABSTRACT TRUNCATED AT 250 WORDS)

Elevated serum concentrations of CA-125 in patients with advanced endometriosis.

CA-125 is a high-molecular-weight glycoprotein that is expressed on the cell surface of some derivatives of embryonic coelomic epithelium. Based on results of an immunoradiometric assay developed to detect CA-125 in peripheral blood, 82% of patients with ovarian cancer and less than 1% of apparently healthy controls have elevated peripheral blood levels of CA-125. Because endometriotic lesions are likely to be derivatives of embryonic coelomic epithelium, the authors investigated serum CA-125 levels in patients with endometriosis. Preoperative serum CA-125 concentrations were measured in 147 patients undergoing diagnostic laparoscopy or laparotomy. Serum CA-125 concentrations were elevated in patients with stage III or IV endometriosis, compared with controls with negative diagnostic laparoscopies (66.5 +/- 14.5 versus 8.20 +/- 0.59 U/ml, mean +/- standard error of the mean; P less than 0.001). Fifty-four percent of patients with stage III or IV endometriosis and 0% of the controls had CA-125 levels greater than 35 U/ml. Occasional patients with stage II endometriosis (13%), leiomyomata uteri (14%), and chronic pelvic inflammatory disease (5%) also had serum CA-125 concentrations greater than 35 U/ml. Immunocytochemical techniques demonstrated the presence of CA-125 on the cell surface of endometriotic lesions.

Recombinant leukocyte alpha interferon in advanced ovarian carcinoma.

Recombinant leukocyte alpha interferon (rIFN-alpha A; Hoffmann-La Roche, Inc) was administered to 15 patients with recurrent or persistent ovarian carcinoma. All patients had been previously treated with surgery and combination chemotherapy including cyclophosphamide (15 patients), doxorubicin (14), and cisplatin (14). Three patient had also previously undergone radiation therapy. At the start of therapy the largest tumor size was less than or equal to 2 cm in four patients and greater than 2 cm in 11. Interferon was administered in three times weekly for 8 weeks at a dose of 20 X 10(6) units/m2, with average drug levels of 2267 pg/ml 6 hours after im injection. In three patients (20%), the dose had to be reduced by 50% because of drug toxicity. Side effects included fever (greater than 101 degrees F) in 12 patients, fatigue in ten, headache in two, diarrhea in two, and reversible myelosuppression in five. Of the 15 patients, one had mixed response lasting 12 weeks, two had stable disease of 8 weeks' duration, and 12 had disease progression.